Ticagrelor-Aspirin versus Clopidogrel-Aspirin among CYP2C19 Loss-of-Function Carriers with Minor Stroke or TIA in Relation to Renal Function: A Post Hoc Analysis of CHANCE-2 Trial

Wang, Anxin; Wang, Yongjun; Xie, Xuewei; Tian, Xue; Claiborne Johnston, S.; Li, Hao; Bath, Philip M.; Zuo, Yingting; Jing, Jing; Lin, Jinxi; Wang, Yilong; Zhao, Xingquan; Li, Zixiao; Jiang, Yong; Liu, Liping; Meng, Xia; Wang, Yongjun

Abstract

Background: Evidence on the risk-benefit ratio of dual antiplatelet therapies among stroke patients with impaired renal function is limited and inconsistent.

Objective: To investigate the effect of renal function on the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin treatment.

Design: Post hoc analysis of a multicenter, randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov: NCT04078737).

Setting: 202 centers in China.

Patients: CYP2C19 loss-of-function allele carriers with minor stroke or transient ischemic attack.

Intervention: Ticagrelor-aspirin and clopidogrel-aspirin.
Measurements: Renal function was evaluated by estimated glomerular filtration rate (eGFR) levels. The primary efficacy and safety outcomes were recurrent stroke and severe or moderate bleeding within 90 days, respectively.

Results: Among 6,378 patients, 4,050 (63.5%) patients had normal (eGFR≥90 mL/min/1.73m2), 2,010 (31.5%) patients had mildly decreased (eGFR 60-89 mL/min/1.73m2), and 318 (5.0%) patients had moderately to severely decreased (eGFR<60 mL/min/1.73m2) renal function. The corresponding differences in recurrent stroke between ticagrelor-aspirin and clopidogrel-aspirin for normal, mildly decreased and moderately to severely decreased renal function was -2.8 percentage point (95% CI, -4.4 to -1.3 percentage point) (hazard ratio [HR], 0.63 [CI, 0.49 to 0.81]), -0.2 percentage point (CI, -2.4 to 2.0 percentage point) (HR, 0.98 [CI, 0.69 to 1.39]), and 3.7 percentage point (CI, -2.3 to 10.1 percentage point) (HR, 1.31 [CI, 0.48 to 3.55]) respectively. Rates of severe or moderate bleeding did not substantially differ by treatment assignments across eGFR categories.

Limitation: Renal function was only evaluated by using eGFR and the proportion of patients with severely decreased renal function was low.

Conclusion: Patients with normal, rather than impaired renal function, received greater benefit from ticagrelor-aspirin versus clopidogrel-aspirin.

Citation

Wang, A., Wang, Y., Xie, X., Tian, X., Claiborne Johnston, S., Li, H., …Wang, Y. (2022). Ticagrelor-Aspirin versus Clopidogrel-Aspirin among CYP2C19 Loss-of-Function Carriers with Minor Stroke or TIA in Relation to Renal Function: A Post Hoc Analysis of CHANCE-2 Trial. Annals of Internal Medicine, 175(11), 1534-1542. https://doi.org/10.7326/M22-1667

• Journal Article Type: Article
• Acceptance Date: Sep 18, 2022
• Online Publication Date: Nov 1, 2022
• Publication Date: Nov 1, 2022
• Deposit Date: Sep 21, 2022
• Publicly Available Date: May 2, 2023
• Journal: Annals of Internal Medicine
• Print ISSN: 0003-4819
• Electronic ISSN: 1539-3704
• Publisher: American College of Physicians
• Peer Reviewed: Peer Reviewed
• Volume: 175
• Issue: 11
• Pages: 1534-1542
• DOI: https://doi.org/10.7326/M22-1667
• Keywords: Alleles; Antiplatelet therapy; Estimated glomerular filtration rate; Hemorrhage; Ischemic stroke; Myocardial infarction; Renal analysis; Safety; Stroke; Transient ischemic attacks
• Public URL: https://nottingham-repository.worktribe.com/output/11466600
• Publisher URL: https://www.acpjournals.org/doi/10.7326/M22-1667